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Our aim was to determine the frequency and characteristics of neurological post-COVID-19 syndrome and the diagnostic and therapeutic measures that were used for the treatment of these patients. Data were collected for 243 patients examined during the period of 11 May 2021 to 22 June 2022. The inclusion criteria were COVID-19 illness and neurological symptoms associated with COVID-19. The exclusion criteria were non-neurological symptoms, patients who did not suffer from COVID-19, and symptoms that occurred after vaccination against the SARS-CoV-2 virus. Data for 227 patients with neurological post-COVID-19 symptoms were analyzed. Most patients presented with multiple symptoms, most often headache, cognitive impairment, loss of smell, paresthesia, fatigue, dizziness, and insomnia. Patients were most often referred for consultative examinations, neuroradiological imaging, and EEG. The therapy was mostly symptomatic. Most patients had no change in their symptoms on follow-up visits (53.21%), while positive outcome was found in 44.95% of patients. This study found that neurological post-COVID-19 syndrome appears to be more common in women, and generally, the most common symptoms are headache and cognitive impairment. The gender distribution of symptoms was clearly visible and should be further investigated. There is a need for longitudinal follow-up studies to better understand the disease dynamic.

Aim: To report the clinical courses of four adolescent patients, who developed childhood-onset schizophrenia and where art had a vital role in diagnosing schizophrenia, monitoring their clinical state and progression. Case report: All of the patients had several diagnoses throughout childhood; however, the final diagnosis was made with the help of art therapy. Following the changes in the content of our patients’ drawings enabled us to notice the changes in their quality of life, functioning, and efficacy of therapy. Some of the patients specified that throughout the drawing process, they felt more satisfied, “better” and not „haunted„ by their hallucinations. This acknowledgment assured us that creative expression through art is an appropriate approach for them. It also strengthened the therapeutic relationship with our patients and encouraged us to understand their disease and make better decisions about their treatment. Conclusions: We propose art as an assistive method in diagnosing schizophrenia. Art can break down communication barriers and can also serve as follow-up method for children and adolescent patients with schizophrenia, Sažetak. Cilj: Prikazati klinički tijek četiriju adolescenata koji su u djetinjstvu oboljeli od shizofrenije, kod kojih je korištenje likovnog izražavanja imalo glavnu ulogu u dijagnosticiranju same bolesti, praćenju kliničkog stanja i progresije. Prikaz slučaja: Tijekom djetinjstva, svim pacijentima dijagnosticirane su brojne dijagnoze, no početkom razdoblja adolescencije, uz pomoć likovnih djela pacijenata, postavljena je konačna dijagnoza shizofrenije. Praćenje likovnih sadržaja crteža pacijenata omogućilo je uvid u promjene kvalitete njihovih života, funkcioniranja i djelotvornosti terapije. Pojedini su naveli kako su se tijekom čitavog procesa crtanja osjećali zadovoljno, „bolje“ i da ih „ne proganjaju“ toliko njihove halucinacije. Ovakvo nas je priznanje uvjerilo da je kreativno izražavanje, kroz artterapiju, odgovarajući pristup bolesti. Terapijski je odnos s našim pacijentima ojačao i potaknuo nas na razumijevanje njihove bolesti i stanja, a ujedno i na donošenje boljih budućih odluka o liječenju. Zaključci: Komunikacija kroz likovno izražavanje može poslužiti kao pomoćna metoda u dijagnosticiranju shizofrenije. Umjetnost može srušiti komunikacijske prepreke, a ujedno može poslužiti i kao metoda praćenja djece i adolescenata sa shizofrenijom

Duboka mozgovna stimulacija (DBS) vodeća je kirurška metoda u liječenju bolesnika s uznapredovanom Parkinsonovom bolešću (PD). Neurorehabilitacijom nakon ugradnje DBS uređaja nastoji se oboljelima omogućiti normalno funkcioniranje u svakodnevnim interakcijama i aktivnostima te na taj način unaprijediti kvalitetu života. U procesu neurorehabilitacije sudjeluje multidisciplinarni tim koji čine neurolog, fizioterapeut i logoped. Uloga neurologa u ovome procesu je prilagođavanje parametara DBS uređaja te prilagodba farmakološke terapije. Uloga fizioterapeuta je održavanje i obnavljanje maksimalne funkcionalne pokretljivosti i sposobnosti, dok je uloga logopeda terapija poremećaja govora na koji DBS ima specifičan utjecaj., Deep brain stimulation (DBS) is the most common surgical treatment for patients with advanced Parkinson’s disease (PD). Following surgery, neurorehabilitation aims to help patients function properly in daily interactions and activities, and thus improve their quality of life. The neurorehabilitation process is overseen by a multidisciplinary team that includes a neurologist, physiotherapist, and speech therapist. The role of neurologist is to change the DBS device’s parameters as well as the pharmacological therapy. The role of the physiotherapist is to maintain and restore maximum functional mobility and ability, while the role of the speech therapist is to assist with speech issues on which DBS can have a significant impact.

Background and objectives The role of coping mechanisms and alcoholism in people affected with malignant tumours of oral cavity and oropharynx is not clearly established in literature. The aim of this study was to compare the coping strategies of the alcohol dependent patients affected by the malignant tumours of oral cavity and oropharynx with the alcohol dependent patients who were not affected by the carcinoma and the healthy population. Methods The study included a total of 153 participants divided into three groups matched in age, gender, education, work and marital status. The first group consisted of 51 alcohol dependent patients diagnosed with malignant tumour of the oral cavity and oropharynx who had been hospitalised and undergone surgery. The second group included 51 patients diagnosed with alcohol dependence but with no cancer diagnosis and the third group consisted of 51 participants who had not previously had any health problems. All participants completed the self- assessment test aimed at registering their usual strategies of coping with stress. Results The three groups of patients differed most in avoidance coping, both on the total score (F(2, 150) = 3, 986 ; p = 0.021) and the following subscales: accepting (F(2, 150) = 5, 509 ; p = 0.005), mental disengagement (F(2, 150) = 4, 017 ; p = 0.020), religion (F(2, 150) = 4, 527 ; p = 0.012), alcohol/drug consumption (F(2, 150) = 11, 825 ; p < 0.001) and isolation (F(2, 150) = 3, 448 ; p = 0.034). Compared to healthy controls, patients diagnosed with malignant tumour and alcohol dependence used more avoidance in coping with stress (p = 0.010). Conclusion Despite the limited generalisation and cross- sectional study design the results indicated that patients affected by alcohol dependency and malignant tumour of oral cavity and oropharynx perceived their illness as something out of their control, something that they can hardly deal with, and mostly relied on disengaging/distancing coping strategies.

Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease, which creates a significant public health burden. There is a challenge for the optimization of therapies since patients not only respond differently to current treatment options but also develop different side effects to the treatment. Genetic variability in the human genome can serve as a biomarker for the metabolism, availability of drugs and stratification of patients for suitable therapies. The goal of this systematic review is to assess the current evidence for the clinical translation of pharmacogenomics in the personalization of treatment for Parkinson’s disease. Methods: We performed a systematic search of Medline database for publications covering the topic of pharmacogenomics and genotype specific mutations in Parkinson’s disease treatment, along with a manual search, and finally included a total of 116 publications in the review. Results: We analyzed 75 studies and 41 reviews published up to December of 2020. Most research is focused on levodopa pharmacogenomic properties and catechol-O-methyltransferase (COMT) enzymatic pathway polymorphisms, which have potential for clinical implementation due to changes in treatment response and side-effects. Likewise, there is some consistent evidence in the heritability of impulse control disorder via Opioid Receptor Kappa 1 (OPRK1), 5-Hydroxytryptamine Receptor 2A (HTR2a) and Dopa decarboxylase (DDC) genotypes, and hyperhomocysteinemia via the Methylenetetrahydrofolate reductase (MTHFR) gene. On the other hand, many available studies vary in design and methodology and lack in sample size, leading to inconsistent findings. Conclusions: This systematic review demonstrated that the evidence for implementation of pharmacogenomics in clinical practice is still lacking and that further research needs to be done to enable a more personalized approach to therapy for each patient.

Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanisms of action. The aim of this study is to characterize the effects of haloperidol, risperidone and aripiprazole on BV-2 microglial cells in in vitro conditions. We have used immunofluorescence and flow cytometry to analyze the classical pro and anti-inflammatory markers, while a real-time metabolic assay (Seahorse) was used to assess metabolic function. We analyzed the expression of p70S6K to evaluate the mTOR pathway activity with Western blot. In this study, we demonstrate the varying effects of haloperidol, risperidone and aripiprazole administration in BV-2 microglial cells. All three tested antipsychotics were successful in reducing the pro-inflammatory action of microglial cells, although only aripiprazole increased the expression of anti-inflammatory markers. Most significant differences in the possible mechanisms of action were seen in the real-time metabolic assays and in the mTORC1 signaling pathway activity, with aripiprazole being the only antipsychotic to reduce the mTORC1 activity. Our results shed some new light on the effects of haloperidol, risperidone and aripiprazole action in microglial cells, and reveal a novel possible mechanism of action for aripiprazole.

Gaucher’s disease type 1 (GD1) is an autosomal recessive disease caused by mutations in the glucocerebrosidase (GBA) gene. We present a case of a 43-year-old man who was diagnosed with GD1 in 2010, and was treated successfully with deep brain stimulation.

As we are facing worldwide pandemic of COVID-19, we aimed to identify potential pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity. Special emphasis will be given on increased susceptibility to infections due to obesity-related low-grade chronic inflammation, higher expression of angiotensin converting enzyme-2 and pathway-associated components, as well as decreased vitamin D bioavailability, since all of them provide easier ways for the virus to enter into host cells, replicate and stunt adequate immune responses., Highlights • COVID-19 susceptibility and severity are increased in obesity. • Identifying pathophysiological mechanisms leading to increased COVID-19 susceptibility and severity in obesity is essential. • Emphasis should be given on low-grade chronic inflammation, higher ACE-2 expression and decreased vitamin D bioavailability.

Background: Suitable biomarkers that have prognostic values are one of the key points of interest in ischaemic stroke. Increased sympathetic nervous system activity in ischaemic stroke causes multiple local and systemic effects that can be detrimental to the outcome. The mechanism of action is increased secretion and activity of catecholamines, whose end metabolic products are vanillylmandelic acid and homovanilic acid. Aim of our study was to determine whether these compounds can be used as potential prognostic biomarkers in ischaemic stroke, as a unique insight into the activity of the sympathetic nervous system. Methods: Urine samples of 96 patients with ischaemic stroke and transitory ischaemic attacks were analysed. Values of vanillylmandelic and homovanillic acids in urine were tested using liquid chromatography on the first and third day post-stroke. Severity of stroke was determined using the NIHSS scale, while functional outcome was determined using the Modified Rankin Scale. Results: Values of vanillylmandelic and homovanillic acids positively correlated with functional outcome of ischaemic stroke. Favorable outcomes correlated with decreased values, on contrary to increased values, which were associated with unfavourable outcomes. Conclusion: Determining the values of these compounds in the urine is an easily available prognostic tool for the ischaemic stroke outcome, while also influencing potential therapeutic changes

OBJECTIVE: The aim of this study was to explore the effectiveness and tolerability of long- acting paliperidone palmitate antipsychotic in adolescent first-episode schizophrenia patients while comparing the results with the oral antipsychotic risperidone. METHODS: This study is a retrospective, noninterventional study to assess the effectiveness and tolerability of long-acting injectable antipsychotic paliperidone palmitate in first-episode adolescent patients during the first 12 months of treatment compared with the oral antipsychotic risperidone. The data include general sociodemographic characteristics, number of hospitalizations, side effects, and the following clinical scales: Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Clinical Global Impression Improvement and Severity (CGI-I and CGI-S), and Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: During the 12- month study period significant improvement was registered in patients receiving both paliperidone palmitate and risperidone in the following scales: PANSS, PSP, CGI-I, and CGI-S. Patients receiving paliperidone palmitate had significantly greater improvement in PANSS, CGI- S, and PSP compared with the risperidone group. Patients receiving risperidone had significantly higher number of hospitalizations than the patients receiving paliperidone palmitate. The TSQM revealed that the patients who were receiving paliperidone palmitate achieved significantly higher scores on the convenience scale, global satisfaction, and on the overall result, whereas no difference was observed on the effectiveness scale. There were several side effects reported for paliperidone (5.5% hyperprolactinemia, 5.5% weight gain) and risperidone (5.5% hyperprolactinemia, 16.7% weight gain). CONCLUSIONS: In conclusion, paliperidone palmitate seems to be safe and effective in adolescent patients. Furthermore, it compared favorably with risperidone in the clinical response, side effects, and hospitalizations.

Anderson-Fabryjeva bolest uzrokovana je nedostatnom aktivnošću enzima α-galaktozidaze A što rezultira nakupljanjem glikosfi ngolipida u lizosomima stanica različitih organskih sustava. Bolest se nasljeđuje X-vezano te je zastupljena u oba spola, no u muškaraca, koji su hemizigoti za mutirani gen, simptomi se ispoljavaju ranije uz izraženiji fenotip. Nakupljanje u stanicama bubrega uzrokuje isprva reverzibilne, a potom i ireverzibilne patološke promjene u svim segmentima nefrona što dovodi do proteinurije i bubrežne disfunkcije s postepenom progresijom do terminalnog stadija bubrežnog zatajenja. U ovom radu osvrnuli smo se na trenutne terapijske mogućnosti u obliku intravenske enzimske nadomjesne terapije agalzidazom alfa i agalzidazom beta uz noviju peroralnu metodu liječenja molekularnim šaperonima. Razmotreni su trenutni dosezi istraživanja genske terapije ugradnjom funkcionalnog GLA gena u genom bolesnika, što je budućnost liječenja nasljednih bolesti. Pravovremeno prepoznavanje i liječenje Anderson-Fabryjeve bolesti značajno smanjuju mortalitet i morbiditet pacijenata te povećavaju njihovu kvalitetu života., Anderson-Fabry disease is a lysosomal storage disorder caused by insufficient α-galactosidase A enzyme activity. It is a hereditary X-linked disease that affects both men and women, although males express more typical symptoms at earlier age since they are hemizygotes for the mutated gene. Accumulation of glycosphingolipids in kidney cells has an impact on all nephron segments and causes proteinuria with progressive renal dysfunction, which can ultimately end in terminal renal failure. In this review of the literature, we present therapeutic options including intravenous enzyme replacement therapy with agalsidase alpha and agalsidase beta and oral treatment with molecular chaperons for patients with amenable mutations. Moreover, we investigated current progress in gene therapy of Fabry disease, which is an evolving field with promising results. Timely recognition and early start of treatment significantly reduces morbidity and mortality of patients with Fabry disease, leading to improved quality of life.

Microglia are resident brain macrophages with key roles in development and brain homeostasis. Cytomegalovirus (CMV) readily infects microglia cells, even as a possible primary target of infection in development. Effects of CMV infection on a cellular level in microglia are still unclear ; therefore, the aim of this research was to assess the immunometabolic changes of BV-2 microglia cells following the murine cytomegalovirus (MCMV) infection. In light of that aim, we established an in vitro model of ramified BV-2 microglia (BV-2∅FCS, inducible nitric oxide synthase (iNOSlow), arginase-1 (Arg-1high), mannose receptor CD206high, and hypoxia-inducible factor 1α (HIF-1αlow)) to better replicate the in vivo conditions by removing FCS from the cultivation media, while the cells cultivated in 10% FCS DMEM displayed an ameboid morphology (BV-2FCS high, iNOShigh, Arg-1low, CD206low, and HIF- 1αhigh). Experiments were performed using both ramified and ameboid microglia, and both of them were permissive to productive viral infection. Our results indicate that MCMV significantly alters the immunometabolic phenotypic properties of BV-2 microglia cells through the manipulation of iNOS and Arg-1 expression patterns, along with an induction of a glycolytic shift in the infected cell cultures.

Cilj: Cilj istraživanja bio jest utvrditi učestalost i karakteristike poslijeoperacijskog poremećaja kognitivnih funkcija (POCD, engl. postoperative cognitive dysfunction) u bolesnika starijih od 18 godina kojima je bio učinjen nekardiokiruški zahvat. Dodatni cilj istraživanja bio je ispitati kognitivne sposobnosti bolesnika prije operacije, 7 dana poslije operacije i 3 mjeseca nakon operacije te utvrditi utječu li dob i komorbiditeti na učestalost POCD-a. Ispitanici i metode: Prospektivnim istraživanjem obuhvaćeno je 63 ispitanika liječenih u Kliničkom bolničkom centru Rijeka. Svaki ispitanik je prije operacije, 7 dana te tri mjeseca nakon operacije ispunio test MoCA. Rezultati: Znakovi POCD-a sedam dana nakon operacije bili su prisutni u 25 (40 %) bolesnika, a tri mjeseca nakon operacije u 8 (13 %) bolesnika. Statistički značajna razlika (p, The primary aim of this study was to establish the incidence and characteristics of postoperative cognitive dysfunction (POCD) in patients undergoing noncardiac surgery. In addition, the aim was to determine whether age and comorbidities have an infl uence on the incidence of POCD. Patients and Methods: Sixty-three patients treated in Rijeka University Hospital Centre completed this prospective study. The following parameters were determined in each patient: age, gender, level of education, chronic illness (hypertension, diabetes and neurologic diseases), type and length of anesthesia, and length and severity of surgical procedure. All patients had normal neurologic and mental state preoperatively. The Montreal Cognitive Assessment (MoCA) test was used to determine cognitive function before surgery, then 7 days and 3 months after surgery. Patients younger than 18 and older than 75 were excluded from the study, as were those suffering from intellectual disability and dementia. Results: Twenty-fi ve (40%) patients had signs of cognitive dysfunction 7 days after surgery, which persisted in 8 (13%) patients 3 months after surgery. There was a significant difference (p

Inhibitori protonske pumpe (IPP) lijekovi su koji su u potpunosti promijenili način liječenja stanja povezanih s pojačanim lučenjem želučane kiseline; peptički ulkus, gastroezofagealna refluksna bolest, funkcionalna dispepsija, gastroprotekcija. Iako su IPP-ovi široko propisivani lijekovi, posljednjih godina povećana pozornost posvećena je potencijalnim neželjenim učincima ovih lijekova. S obzirom na to da sve veći broj pacijenata prima IPP-ove kao dio kronične terapije za bolesti i stanja koja su povezana s pojačanim lučenjem želučane kiseline, dugoročni potencijalno štetni učinci ove skupine lijekova dobivaju sve veću pozornost, pri čemu većina istraživanja upućuje na to da su određeni pacijenti u skupini s povećanim rizikom., Proton pump inhibitors (PPI) are the drugs that have brought a revolution as a treatment of choice for various conditions associated with increased secretion of gastric acid; peptic ulcers, gastroesophageal reflux disease, functional dyspepsia. Although PPIs are widely prescribed and generally safe drugs, recently increased attention was focused on the potential adverse effects of these drugs. Given the increasing number of patients receiving PPI’s, long-term potential adverse effects of this class of drugs are gaining increasing attention. However, most of recent investigations raise the possibility that elderly and malnourished patients have a higher risk for these side effects.

Cortical gray matter loss in schizophrenia remains a great therapeutic difficulty. Each psychotic episode causes irreversible cortical gray matter loss, that causes the patients to never regain their previous state of functioning. Microglial cells are part of the innate immune system and their functions, among others, include phagocytosis and release of neurotrophic factors. They have a key impact on developmental and plasticity-induced removal of neuronal precursors, live-but-stressed neurons and synapses, while also stimulating synaptic growth and development. We hypothesize that microglia are the culprit for the cortical gray matter loss in schizophrenia through abnormal synaptic pruning, phagocytosis of stressed neurons and lacking neurotrophic factor release. Furthermore, we propose a research that could validate the hypotheses using serum samples of first-episode early-onset patients. By measuring the serum levels of milk fat globule-EGF factor 8 (MFG-E8), subcomponent in the classical pathway of complement activation (C1q), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and interleukin-10 (IL-10), we could gain an insight into the state of microglial activation during various stages of the disease. If this hypothesis is valid, new targeted drugs could be developed in order to reduce the deterioration of cortical gray matter, thereby possibly improving negative symptoms and cognitive deficits.

vAlentIno RACKI1, nIKA GRžetA2, KRIstInA JuRdAnA3, JAsenKA mRSIc-pelCIc4, nAtAlIA KuCIc5 1unIveRsIty of RIJeKA, fACulty of medICIne, RIJeKA, CRoAtIA 2unIveRsIty of RIJeKA, fACulty of medICIne, depARtment of physIoloGy And ImmunoloGy, RIJeKA, CRoAtIA 3unIveRsIty of RIJeKA, depARtment of bIoteChnoloGy, RIJeKA, CRoAtIA 4unIveRsIty of RIJeKA, fACulty of medICIne, depARtment of phARmAColoGy And toxIColoGy, RIJeKA, CRoAtIA 5unIveRsIty of RIJeKA, fACulty of medICIne, depARtment of physIoloGy And ImmunoloGy, RIJeKA, CRoAtIA

Introduction: Microglia are a subset of macrophages permanently present in the central nervous system. Apart from being the key effector of the innate immune response, microglia play a major role in the maintenance of homeostasis. They represent the first line of defense in the central nervous system and as such are affected by all changes in their environment. Microglia respond to hypoxia with acute inflammation, followed by a tendency for an anti-inflammatory switch during the late post-hypoxia period. Celastrol, a naturally occurring quinone methide triterpene derived from the Thunder of God Vine is a pleiotropic compound showing anti-inflammatory, anti-tumor, anti-hypertensive and anti-diabetic activity in numerous cellular and in vivo models. The aim of our research was to determine the effects of celastrol on microglial cells exposed to in vitro hypoxic conditions. Materials and methods: We used murine microglial BV-2 cell line which is commonly used as a substitute for primary microglia. The cells were treated with 100nM of celastrol before or after hypoxia (